Project Summary This proposal outlines a 3-year post-doctoral fellowship, designed to provide interdisciplinary training for an independent research career at a major research university. The applicant?s interests involve understanding the biological mechanisms by which stressful experiences affect perinatal outcomes. Previous research has repeatedly shown that women who experience stressful life events during pregnancy are at increased risk of adverse birth outcomes, including preterm birth and abnormal fetal growth. However, the biologic pathways that underlie this relationship continue to be poorly understood. The applicant?s long-term research goal is to clarify these mechanisms through interdisciplinary research. Accordingly, she proposes a fellowship with training in health psychology, fetal development, and placental biology, overseen by a team of mentors with expertise in these distinct fields, who are already collaborating on two major NIH-funded projects. The research plan includes three aims, which use different strategies to address the relationships among stressful life events during pregnancy, maternal inflammation, placental function, and birth outcomes. Aim 1 investigates links between life events and adverse birth outcomes, including preterm birth and poor fetal growth. Mediation by inflammatory markers in maternal serum will also be explored. Aim 2 evaluates the impact of the assassination of President John F. Kennedy, a stressful event for many Americans, on birth outcomes and examines mediation by placental inflammatory and vascular lesions. To gain stronger evidence for causal inference, this relationship will also be examined in siblings discordant for exposure. Aim 3 investigates cellular mechanisms, and considers whether life events facilitate placental infiltration of maternal immune cells. In addition, the known timing of the events relative to pregnancy in all three aims enables the investigation of critical windows. Collectively, the results will help to elucidate how stress may affect pregnancy outcomes, which may be useful for developing interventions. Further, understanding how stress impacts pregnancy is increasingly important as studies have reported intergenerational effects that may predispose future generations to adverse outcomes. The research is part of a broader training program that will supplement the applicant?s background in perinatal epidemiology. Through this training, the applicant will (1) develop expertise in the conceptualization and measurement of key constructs in health psychology, (2) gain exposure to the clinical management of adverse pregnancy outcomes, and (3) develop expertise in laboratory tools for evaluating placental pathology. To accomplish these goals, the applicant will complete relevant coursework and will gain hands-on training by working with her co-sponsors, who are experts in these areas. In addition, the applicant will participate in professional development activities, including conference participation and training in research ethics and grant writing. This training, in combination with the applicant?s background, will prepare her for career as a PI conducting multidisciplinary research to investigate how maternal stress affects pregnancy outcomes.